Temple Therapeutics Reveals Breakthrough Findings on Ovarian Cancer at AACR 2023

 

Temple Therapeutics, a biotechnology company pioneering a female-focused precision medicine approach, presented new in vitro and in vivo data on TTX335o, the first drug candidate from the company’s platform that won the Eurostar Eureka peer-reviewed grant process in 2019 for ovarian cancer, and the novel ovarian cell target, lemur tyrosine kinase 3 (LMTK3). The new data was provided at a poster presentation at the American Association of Cancer Research (AACR) Annual Meeting, which took place on April 14-19, 2023 in Orlando.

 

“While survival rates for ovarian cancer are creeping up to the 50% level, it is clear that the vast majority of women are diagnosed too late,” said Sanj Singh, CEO of Temple Therapeutics. “It has been referred to as the silent killer by some, and others have described it as the neglected or ignored killer. Despite its lethality as the most dangerous gynecological cancer, the field has been sparsely researched. We are changing that. As we recognize World Ovarian Cancer Day today, we can do better. Our sisters, aunts, spouses, friends, co-workers, mothers, and grandmothers are affected.”

 

TTX335o is based on the breakthrough discovery of LMTK3 and its mechanism of action. Increased levels of LMTK3 have been shown to affect the transcription of genes promoting DNA repair, cell viability, and tumorigenesis which activates cell death pathways specific to cancer cells without harming normal cells.

 

Preclinical data presented at AACR 2023 included:

 

• LMTK3 protein was detected in 98% of ovarian cancer tissues collected from 204 patients in various stages and major histology and localized in the nucleus of health cells and in the cytoplasm of tumor cells.
• Risk of death among ovarian cancer patients with more cytoplasmic than nuclear LMTK3 levels was particularly high during the first year after diagnosis. This suggests cytoplasmic LMTK3 expression correlates with poor survival which serves as a potential prognostic marker for ovarian cancer patient outcomes (p<.01).
• TTX335o specifically targets apoptosis, a major determinant in uncontrolled cell growth in ovarian cancer through a novel integrin (αV/β1), monomeric myeloperoxidase (mMPO), and LMTK3 signaling pathways. Knocking down LMTK3 also induced cell death in ovarian cancer, and more importantly, did not harm normal cells.
• In vitro and in vivo studies seem to validate LMTK3 as a specific target and predictor of clinical outcomes in ovarian cancer.

Both nuclear and cytoplasmic LMTK3 expressions correlated with tumor grade and patient survival in cancers such as breast and colorectal cancer. The clinical significance of the LMTK3 gene was tested from 204 early-stage (stage I-II) ovarian cancer patients of all major subtypes. Results from this study revealed a higher cytoplasmic to nuclear localization of LMTK3 correlated with worse overall survival (P<0.01). More importantly, engineered novel target-specific molecules, collectively known as TTX335o, significantly induced ovarian cancer cell death. Strikingly, TTX335o molecules are also effective in cells resistant to chemotherapy (e.g., docetaxel or cisplatin) as in sensitive cells.

 

“The discovery of this novel target almost five years ago was surprising and exciting because we thought, what if this could be an early detection biomarker,” said Dr. Ghassan Saed, Inventor and Lead Researcher and Associate Professor of Gynecology Oncology at Wayne State University and Karmanos Cancer Center in Michigan. “Dr. Helou at Sahlgrenska Cancer Center screened the target across 204 Stage I-II ovarian cancer patient samples and saw firsthand the correlation data of expression of the target and poor prognosis. We knew then this may be a game changer for ovarian cancer because it was present in all major subtypes. We saw the potential for a novel biomarker and an associated target. We developed TTX335o to specifically target LMTK3 pathways that kill tumors without harming normal cells, even at high doses.”

 

“Treatment with TTX335o and other modalities, like siRNA, significantly induced the killing of both chemosensitive and chemoresistant ovarian cancer cells without affecting normal cells in vitro,“ said Anna Portela, CEO of Xenopat, a spin-off of the Catalan Institute of Oncology (ICO), the Bellvitge Biomedical Research Institute (IDIBELL), and the Bellvitge University Hospital (HUB). “Moreover, we observed this killing as synergistic with both Cisplatin and Taxotere treatment in vitro. We used an A2780 cell line-derived orthotopic xenograft mouse model of ovarian cancer to test the efficacy of specific TTX335o in vivo. Strikingly, TTX335o 20 mg/kg IV dose given in the same dosing schedule and duration as cisplatin showed a 35% tumor reduction. More importantly, in vivo safety studies showed no signs of toxicity of TTX335o, even at a very high dose of 40 mg/kg. With molecule, dose, and schedule optimization in ongoing experiments, we could expect a higher efficacy.”

 

“We have generated a substantial amount of preclinical data demonstrating TTX335o is unlike any other targeted therapy for ovarian cancer or approach,” said Dr. Neil Sankar, Chief Medical Officer at Temple Therapeutics. “The addition of a companion diagnostic for early detection, therapeutic impact, and disease progression injects much-needed hope for ovarian cancer patients. Earlier diagnosis and intervention improve patient outcomes. It seems that this target is agnostic across the major histological subtypes which helps to serve the 80% of ovarian cancer patients who do not have the BRCA genes (BReast CAncer).”

 

Follow the World Ovarian Cancer Coalition on Twitter @ovariancancerco and #NoWomanLeftBehind.

 

The AACR 2023 poster is available upon request at info@templerx.com.

 

**About Temple Therapeutics      

Temple Therapeutics is a clinical-stage, privately held biotechnology company pioneering a female-focused precision medicine approach for the discovery, development, and commercialization of novel therapeutics and companion diagnostics for early detection and treatment of profibrotic gynecological and related disorders. Temple’s mission is inspired by a belief that medical progress must be available to all, serving the underserved women’s health population and providing access to effective and safe treatment options through our focus on research and new health technologies. Temple Therapeutics’ current pipeline spans endometriosis, ovarian cancer, and related disorders of abdominal tissue fibrosis. With the goal of becoming a leading Ob/Gyn biopharma, our vision is for a world in which gynecological health is destigmatized, early diagnostics lead to less invasive treatments, and healthcare is accessible and holistic—addressing physical, mental, and social well-being. For more information, visit www.templerx.com and follow on LinkedIn.

 

 

Delaying treatment for localised prostate cancer does not increase mortality risk, trial shows

 

Active monitoring of prostate cancer has the same high survival rates after 15 years as radiotherapy or surgery, reports the largest study of its kind today.  The latest findings from the ProtecT trial are presented today at the European Association of Urology (EAU) Congress in Milan and published in the New England Journal of Medicine. Although men on active monitoring – which involves regular tests to check on the cancer – were more likely to see it progress or spread than those receiving radiotherapy or surgery, this didn’t reduce their likelihood of survival. The trial also found that the negative impacts of radiotherapy and surgery on urinary and sexual function persist much longer than previously thought – for up to 12 years. The findings show that treatment decisions following diagnosis for low and intermediate risk localised prostate cancer do not need to be rushed, according to lead investigator, Professor Freddie Hamdy from the University of Oxford. “It’s clear that, unlike many other cancers, a diagnosis of prostate cancer should not be a cause for panic or rushed decision making,” he said. “Patients and clinicians can and should take their time to weigh up the benefits and possible harms of different treatments in the knowledge that this will not adversely affect their survival.” The trial, funded by the National Institute for Health and Care Research, was led by researchers at the Universities of Oxford and Bristol in nine UK centres and is the longest running study of its kind. It is the first to fully evaluate three major treatment options: active monitoring, surgery (radical prostatectomy) and radiotherapy with hormones for men with localised prostate cancer. Between 1999 and 2009, 1,643 men aged 50-69 years across the UK, who were diagnosed with localised prostate cancer after a PSA blood test, agreed to be randomised to active monitoring (545), radical prostatectomy (553) or radical radiotherapy (545). The research team followed the men over an average of 15 years, to measure mortality rates, cancer progression and spread, and the impact of treatments on quality of life. They found that around 97% of the men diagnosed with prostate cancer survived 15 years after diagnosis, irrespective of which treatment they received. Around a quarter of the men on active monitoring had still not had any invasive treatment for their cancer after 15 years. Patients from all three groups reported similar overall quality of life, in terms of their general mental and physical health. But the negative effects of surgery or radiotherapy on urinary, bowel and sexual function were found to persist much longer than previously thought. In earlier findings released in 2016, the researchers found that, after ten years follow up, men whose cancer was being actively monitored were twice as likely to see it progress or metastasise than those in the other groups. The assumption had been that this might lead to a lower survival rate for men on active monitoring over a longer time period. However, the results from the 15-year follow up show that this isn’t the case and that survival rates remain similarly high across all groups. Lead investigator, Professor Freddie Hamdy from the University of Oxford, said: “This is very good news. Most men with localised prostate cancer are likely to live for a long time, whether or not they receive invasive treatment and whether or not their disease has spread, so a quick decision for treatment is not necessary and could cause harm.” “It’s also now clear that a small group of men with aggressive disease are unable to benefit from any of the current treatments, however early these are given. We need to both improve our ability to identify these cases and our ability to treat them.” Co-investigator, Professor Jenny Donovan, from the University of Bristol, said: “Patients and doctors now have the necessary information on the long-lasting side effects of treatments to better understand the trade-offs between their benefits and harms. Survival no longer needs to be considered when deciding on treatment – as that’s the same for all three options. Now men diagnosed with localised prostate cancer can use their own values and priorities when making the difficult decisions about which treatment to choose.” The trial has also highlighted flaws in current methods to predict which prostate cancers are likely to grow quickly and spread. Initially, all those recruited to the trial were diagnosed with localised cancer and 77% of them were deemed low risk. A reassessment using more modern methods showed that a far greater number would now be considered intermediate-risk – and in around 30% of men, the disease had spread beyond the prostate already. This means that the participants in the study had higher grade and stage disease than was thought initially. Despite this finding, mortality was still low, even when men with intermediate disease delayed or did not have radical treatment. Some of the men who subsequently died of their prostate cancer had been assessed as low risk at diagnosis, which the researchers highlight as an issue of concern. Professor Peter Albers, chair of the EAU’s Scientific Congress Office and a urologist at Düsseldorf University, said: “The fact that the greater progression of disease seen under active monitoring didn’t translate into higher mortality will be both surprising and encouraging to urologists and patients. Active monitoring and biopsy protocols today are much more advanced than at the time this trial was conducted, so it’s possible we could improve on these outcomes still further. It’s an important message for patients that delaying treatment is safe, especially as that means delaying side effects as well.” “But it’s also clear that we still don’t know enough about the biology of this disease to determine which cancers will be the most aggressive and more research on this is urgently needed.”

Quirónsalud Campo de Gibraltar implanta el Servicio de Teledermatología con entrega de diagnóstico en un plazo de 24-48 horas

 

Agilidad en la atención al paciente, fiabilidad del diagnóstico y  detección precoz.      

Estas tres premisas han impulsado la puesta en marcha del Servicio de Teledermatología, el último proyecto asistencial impulsado desde el Hospital Quirónsalud Campo de Gibraltar y el Centro Médico Quirónsalud Algeciras.

 

En ambos centros se ha anunciado la implantación de este nuevo sistema que garantiza la evaluación de lesiones dermatológicas por un especialista en un plazo de entre 24 y 48 horas.

Este procedimiento agiliza sustancialmente los plazos actuales de diagnóstico y, en consecuencia, supone una gran ventaja para el paciente quien tendrá a su disposición un diagnóstico profesional en un periodo muy corto de tiempo. “Cuando el paciente solicita una consulta para evaluar una lesión en la piel, se le agenda una cita en la que un técnico de Diagnóstico de Imagen o enfermero con formación específica para esta labor toma una fotografía de la zona a analizar mediante un dermatoscopio. Inmediatamente, esta imagen es incluida en una plataforma digital a la que tiene acceso el dermatólogo quien evaluará y diagnosticará la lesión dérmica”, explica el director médico del hospital gaditano, el doctor Mathieu Alain Juvin.

Una vez obtenido el diagnóstico, el especialista prescribe el tratamiento a seguir con lo que se da repuesta inmediata al paciente. “En otros casos, se gestiona al momento una segunda cita para una evaluación en profundidad en la consulta de Dermatología. También existe una tercera posibilidad, la de agendar una intervención inminente, para aquellos casos en los que se detecte la necesidad de intervenir en el área cuanto antes”, matiza el responsable médico.

Tecnología avanzada de precisión El dermatoscopio digital utilizado en la consulta el Hospital Quirónsalud Campo de Gibraltar y el Centro Médico Quirónsalud Algeciras para tomar la imagen de la lesión en la piel dispone de un software específico para la captación de fotografías más detalladas y con mayor información.

 Esta nueva tecnología ha sido diseñada para el diagnóstico clínico ya que permite observar en profundidad las distintas capas de la piel.

La diferencia principal respecto a la fotografía convencional digital es que incluye una iluminación especial que permite obtener una visión tridimensional del área a analizar que facilita la evaluación por parte del profesional ya que puede determinar la presencia de células atípicas en la epidermis.

Los principales tipos de cáncer de piel son: carcinoma de células basales, carcinoma de células escamosas y melanoma. Según el Observatorio de la Asociación Española Contra el Cáncer (AECC), en España los carcinomas de piel tuvieron una una tasa de incidencia de 47 casos por 100.000 habitantes en el año 2020. En lo que llevamos de año se han detectado más de 22.2oo casos de cánceres de piel no melanoma.

Blueprint Medicines Data Highlight Clinical Leadership in Systemic Mastocytosis at AACR Annual Meeting 2021

 Blueprint Medicines Corporation (NASDAQ: BPMC) today announced that multiple presentations across the company's leading systemic mastocytosis (SM) program are being reported at the virtual American Association for Cancer Research (AACR) Annual Meeting 2021. The presentations focus on registrational PATHFINDER trial data of AYVAKIT™ (avapritinib) in advanced SM, PIONEER Part 1 data highlighting the impact of AYVAKIT on skin manifestations of SM, and Phase 1 trial data for BLU-263, a next-generation KIT D816V inhibitor. Blueprint Medicines is developing AYVAKIT for advanced and non-advanced SM, and BLU-263 to further address the range of  tient needs in non-advanced SM and other mast  cell disorders.

"Data reported at AACR reflect our commitment to transform treatment for patients living with systemic mastocytosis," said Becker Hewes, M.D., Chief Medical Officer at Blueprint Medicines. "In the PATHFINDER trial, AYVAKIT had high response rates consistent with EXPLORER trial data, reinforcing the profound clinical benefits that can be achieved by precisely targeting the underlying driver of disease. For BLU-263, data in healthy volunteers showed a well-tolerated safety profile and support our plans to initiate the Phase 2/3 HARBOR study, which expands our development efforts into a broader population of patients with non-advanced SM. We are currently on the precipice of our first potential approval in advanced SM, and we are committed to working closely with the SM community so we may meet the needs of patients as quickly as possible."

AYVAKIT – Highlights from the Registrational Phase 2 PATHFINDER Trial

In a pre-specified interim analysis from the PATHFINDER trial, 32 patients who primarily received a starting dose of 200 mg once daily were evaluable for response, as of a data cutoff date of June 23, 2020. Combined with Phase 1 EXPLORER trial results, these data support Blueprint Medicines'marketing applications in advanced SM under review in the U.S. and Europe. Overall, 75 percent (95% CI: 57%, 89%) of patients had a confirmed response, which was defined as complete remission with full or partial recovery of peripheral blood counts (CR/CRh), partial remission or clinical improvement. The median time to response was two months, and all responses were ongoing at a median follow-up of 10.4 months. The CRh rate was 19 percent, with a median time to CRh of 5.6 months. These results show that responses deepened over time at a rate consistent with the EXPLORER trial.

AYVAKIT led to robust and durable benefits across a number of additional clinical activity measures. In new patient-reported outcomes data, AYVAKIT showed a statistically significant reduction in total symptom score after 40 weeks (p<0.001), as measured by the Advanced Systemic Mastocytosis Symptom Assessment Form. Treatment with AYVAKIT resulted in robust improvements in patient-reported quality of life, based on the European Organization for Research and Treatment of  Cancer   Quality of Life Questionnaire. Across multiple measures of mast cell burden, AYVAKIT showed profound reductions in serum tryptase, bone marrow mast cells, KIT D816V allele burden and spleen volume.

Consistent with previously disclosed data, AYVAKIT was generally well-tolerated in 62 patients enrolled in the PATHFINDER trial, and most adverse events (AEs) were reported as Grade 1 or 2. The most common AEs (≥15 percent) were peripheral edema, periorbital edema, thrombocytopenia, anemia, neutropenia, diarrhea, nausea, vomiting and fatigue. Three patients (5 percent) discontinued AYVAKIT due to treatment-related AEs, and most patients (84 percent) have remained on treatment as of the data cutoff date.

"These data reinforce the potential of avapritinib to improve the standard of care for patients with advanced systemic mastocytosis, a disease characterized by organ damage due to mast cell infiltration," said Daniel DeAngelo, M.D., Ph.D., Chief of the Division of Leukemia at Dana-Farber Cancer Institute. "I am highly encouraged by the rapid and durable responses shown across multiple measures of mast cell burden, patient-reported symptoms as well as quality of life. Furthermore, avapritinib was generally well-tolerated, with 5 percent of patients discontinuing due to treatment-related adverse events. Since avapritinib is able to selectively target the primary driver of the disease, it has the potential to fundamentally change the outlook for patients with advanced SM."

AYVAKIT – Statistically Significant Reductions of Aberrant CD30-Positive Mast Cells in Skin Lesions Shown in Phase 2 PIONEER Trial

In non-advanced SM, skin symptoms frequently persist and can severely impact quality of life. To assess the effects of AYVAKIT on mast cell burden in skin lesions, skin biopsies were obtained at baseline and week 12 in Part 1 of the PIONEER trial. Immunohistochemistry tests were performed to determine the proportion of aberrant mast cells in skin tissue, based on expression of CD25, CD30 and other transmembrane receptors observed in SM. Skin lesional tissue at baseline had more CD30-positive than CD25-positive mast cells. Following 12 weeks of treatment, AYVAKIT significantly reduced the proportion of aberrant CD30-positive mast cells in skin lesions compared to placebo (p=0.0082), as of a data cutoff date of December 4, 2020. These data expand on previously reported results showing the impact of AYVAKIT on skin manifestations of SM, and suggest that CD30 may be an important biomarker of aberrant mast cells in SM-related skin lesions.

BLU-263 – Safety and Pharmacokinetics Profile from Phase 1 Trial in Healthy Volunteers

A placebo-controlled, Phase 1 trial evaluated the safety, tolerability and pharmacokinetics of BLU-263 in healthy volunteers. This AACR presentation reported on single ascending dose cohorts (15 to 200 mg doses) and multiple ascending dose cohorts (25 to 100 mg once-daily doses for ten consecutive days), as of a data cutoff date of November 9, 2020. BLU-263 was well-tolerated across all doses studied, and all AEs were reported as Grade 1. Pharmacokinetic data showed dose-dependent increases in systemic exposure of BLU-263, with the half-life of BLU-263 supporting once-daily dosing. Based on these results, the company plans to evaluate BLU-263 at doses ranging from 25 to 100 mg once daily in Part 1 of the Phase 2/3 HARBOR trial in patients with non-advanced SM, which the company plans to initiate in mid-2021.

MAYOR SUPERVIVENCIA GLOBAL EN EL CÁNCER DE PRÓSTATA AVANZADO GRACIAS A LOS AVANCES TERAPÉUTICOS

La supervivencia en cáncer de próstata avanzado en los últimos 15 años se ha triplicado gracias al desarrollo de nuevos agentes hormonales, quimioterapia o radiofármacos, pasando de 12-18 meses en 2005, cuando sólo se disponía de quimioterapia, a los 32-36 meses actuales. Además, los inhibidores de PARP han demostrado beneficio en supervivencia en pacientes con cáncer de próstata avanzado, previamente tratados con otras líneas de tratamiento y alteraciones en genes implicados en la reparación del DNA, siendo los más frecuentes BRCA1 y BRCA. Por su parte, las combinaciones de nuevos fármacos con agentes inmunoterápicos representa otra prometedora estrategia terapéutica en el cáncer de próstata avanzado.

En pacientes con carcinoma de próstata resistente a la castración que todavía no han desarrollado metástasis, diferentes agentes hormonales de nueva generación han demostrado retrasar la aparición de metástasis en aproximadamente dos años, disminuir el riesgo de aparición de síntomas en más de un 50% y, además, en el Congreso de la Sociedad Americana de Oncología Médica (ASCO) recientemente celebrado, han demostrado ser capaces de mejorar la supervivencia de los pacientes.

En el marco de la campaña de comunicación “En Oncología cada AVANCE se escribe en Mayúsculas”, SEOM da a conocer la evolución y LOS avances médicos que se han sucedido en estas últimas décadas en el tratamiento de los diferentes tumores. Coincidiendo con el Día Mundial del Cáncer de Próstata que se celebra este jueves, 11 de junio, destacamos los avances más importantes en cáncer de próstata, el segundo cáncer más diagnosticado en nuestro entorno (primero en varones), con una estimación de 35.126 nuevos casos en España en 2020, según el informe de SEOM “Las cifras del cáncer en España” de 2020.  

Además, el cáncer de próstata es el tumor de mayor prevalencia en varones con una estimación para el año 2018 de 106.941 pacientes afectos (25,8%), según los últimos datos disponibles recogidos en el citado informe de SEOM. Sin embargo, ocupa el tercer lugar como responsable del número de fallecimientos por cáncer en varones en España, habiéndose reducido la tasa de mortalidad un 1,6% en 2018 respecto a 2017. La supervivencia neta a cinco años de los pacientes diagnosticados en el periodo 2008-2013 fue de 89,8%, la más elevada entre los tumores frecuentes.

En la actualidad, la inmensa mayoría de casos de cáncer de próstata se diagnostica en estadios iniciales, mientras que sólo el 5-10% corresponde a casos avanzados (metastásicos) al diagnóstico. En estadios iniciales, el cáncer de próstata es curable en una gran mayoría de casos mediante técnicas actuales de cirugía, radioterapia / braquiterapia con o sin la adición de hormonoterapia.

En una proporción de casos, sin embargo, la enfermedad desarrolla resistencia al tratamiento hormonal (resistencia a la castración) con el eventual desarrollo de metástasis, situación denominada cáncer de próstata resistente a la castración metastásico. En otras ocasiones, sin embargo, los pacientes presentan metástasis en el momento del diagnóstico, situación denominada cáncer de próstata hormono sensible metastásico, no subsidiario ya de opciones curativas como la cirugía y la radioterapia. En estos casos, los objetivos del tratamiento son prolongar la supervivencia, preservar la calidad de vida y prevenir eventos óseos.

Es en estos casos avanzados (resistencia a la castración y enfermedad hormonosensible metastásica) donde se ha realizado la mayoría de avances en el tratamiento de la enfermedad. Entre los años 2011 y 2014, el desarrollo de nuevos agentes hormonales (abiraterona, enzalutamida), quimioterapia (cabazitaxel) o radiofármacos (Ra-223) ha permitido aumentar la supervivencia desde los 12-18 meses en 2005, cuando sólo estaba disponible la quimioterapia con docetaxel, a los 32-36 meses actuales. Además, en el último año, se han presentado los resultados de un estudio fase III con olaparib, un inhibidor de PARP, que ha demostrado beneficio en supervivencia en pacientes con cáncer de próstata avanzado y previamente tratado con otras líneas de tratamiento y alteraciones en genes implicados en la reparación del DNA, siendo los más frecuentes BRCA1 y BRCA2. Otros inhibidores de PARP como rucaparib, talazoparib o niraparib, están siendo también estudiados en otros contextos del cáncer de próstata, tanto en monoterapia como en combinación con otros fármacos. Por otro lado, las combinaciones de nuevos fármacos con agentes inmunoterápicos representa otra prometedora estrategia terapéutica en el cáncer de próstata avanzado, actualmente en evaluación dentro de ensayos clínicos.

Por otro lado, en pacientes con carcinoma de próstata resistente a la castración que todavía no han desarrollado metástasis, tanto apalutamida como enzalutamida y darolutamida, todos ellos nuevos agentes hormonales, han demostrado retrasar la aparición de metástasis en aproximadamente dos años, disminuir el riesgo de aparición de síntomas en más de un 50% y, además, en el Congreso de la Sociedad Americana de Oncología Médica recientemente celebrado, han demostrado ser capaces de mejorar la supervivencia de los pacientes.

Además, nuevos estudios han confirmado el valor del tratamiento tanto de quimioterapia como de estos nuevos agentes hormonales, como la abiraterona, enzalutamida o apalutamida, en combinación con la deprivación androgénica (hormonoterapia), en pacientes con enfermedad metastásica al diagnóstico. A través de diferentes ensayos clínicos, estos agentes han demostrado una reducción del riesgo de muerte de hasta un 38%, incluso en pacientes de alto riesgo, y un incremento de la mediana de supervivencia desde los 32 hasta los 50 meses.

La cirugía robótica, frente a la convencional, mejora especialmente el pronóstico del cáncer de próstata en los pacientes con sobrepeso

   

 En el último año, MD Anderson Cancer Center Madrid ha realizado casi 150 intervenciones con el Da Vinci Xi, destacando varias cirugías de rescate tras radioterapia

En los últimos años, los resultados en supervivencia y calidad de vida de los pacientes con cáncer de próstata han mejorado mucho no solo gracias a un diagnóstico cada vez más precoz y al estudio de nuevas opciones terapéuticas, sino también gracias a los importantes avances en cirugía oncológica. “La cirugía robótica mejora el pronóstico de los pacientes gracias a que nos permite reducir los márgenes quirúrgicos y realizar linfadenectomías más amplias”, explica el doctor Carlos Núñez, jefe del Servicio de Cirugía Urológica de MD Anderson Madrid, quien señala también que estos mejores resultados se aprecian sobre todo en los pacientes con sobrepeso.  

Con motivo del Día Mundial del Cáncer de Próstata, que se conmemora el próximo jueves 11 de junio, este especialista quiere poner de manifiesto la importancia de la cirugía robótica en la mejora de los resultados obtenidos en los pacientes con este tumor. “La cirugía robótica permite una mejor visión que la cirugía convencional (la cirugía abierta), manteniendo e incluso mejorando la maniobrabilidad de la mano del cirujano, incluso en espacios pequeños, con respecto a la laparoscopia”, asegura el doctor Núñez.

Una ventaja fundamental que, en su opinión, se traduce en tres mejoras clave. En primer lugar, al reducirse los márgenes positivos, los resultados oncológicos son superiores “sobre todo en los casos en los que se realiza preservación neurovascular”, explica este profesional. Además, al ser la disección de estos haces neurovasculares mucho más precisa, la segunda mejora importante es que se reducen mucho los casos posteriores de impotencia y, en parte, los de incontinencia. 

Sobre la incontinencia, el doctor Núñez aclara que también existe una clara reducción de casos, la tercera mejora, pero sobre todo debido a que “la visión de la zona esfinteriana es muy superior a la que tenemos en cirugía abierta”, explica el doctor Núñez.

La reducción de casos de impotencia e incontinencia urinaria tras una intervención quirúrgica en estos pacientes no solo mejora mucho su calidad de vida, sino que permite una recuperación mucho más rápida. “Esto logra también que el impacto psicológico en los pacientes sea mucho menor”, resalta este especialista. 

MD Anderson Madrid ha realizado ya casi 150 cirugías con el robot Da Vinci Xi 

En el último año, MD Anderson Madrid ha realizado ya casi un total de 150 procedimientos con el robot Da Vinci Xi y ha obtenido unos resultados que el jefe del Servicio de Cirugía Urológica del centro califica de “extraordinarios”. Además de intervenciones más habituales, el doctor Núñez destaca sobre todo “varios casos de cirugía de rescate tras radioterapia, unas intervenciones que suponen un auténtico reto quirúrgico para nosotros”. 

De cara al futuro, la cirugía robótica se prepara para trabajar con un puerto único, de forma que se reduzca el número de pequeñas incisiones que se realizan en el abdomen, un avance que, destaca el doctor Núñez, “puede resultar clave en patologías en las que la estética tenga mucha importancia”. En cáncer de próstata, este experto cree que el futuro va a ir más enfocado a “aligerar y reducir el tamaño de los brazos robotizados con el objetivo de disminuir la interferencia entre los mismos y mejorar así la maniobrabilidad”.

PharmaMar presenta resultados de trabectedina y doxorubicina en primera línea de tratamiento de leiomiosarcomas en el congreso de ASCO 2020

PharmaMar (MSE:PHM) anuncia que, durante la reunión anual de la Sociedad Americana de Oncología Clínica (ASCO, American Society of Clinical Oncology), que se ha celebrado del 29 al 31 de mayo de 2020, se han presentado en Oral Abstract Session los resultados finales del estudio de fase II de trabectedina en combinación con doxorubicina para el tratamiento de pacientes con leiomiosarcoma uterino y de tejidos blandos metastásico avanzado.

Bajo el título “A single-arm multicenter phase II trial of doxorubicin (Doxo) in combination with trabectedin (Trab) given as first-line treatment to patients with metastatic/advanced uterine (U-LMS) and soft tissue leiomyosarcoma (ST-LMS): Final results of the LMS-02 study” (Abstract 11506), la Dra. Patricia Pautier, del Departamento de Oncología Médica, Instituto Gustave Roussy, Villejuif, Francia, ha concluido que trabectedina en combinación con doxorubicina es un tratamiento efectivo en primera línea para pacientes con leiomiosarcoma.

El estudio alcanzó los objetivos primario y secundarios, con una mediana de Supervivencia Libre de progresión (PFS, Progression-Free Survival) de 10,1 meses; una mediana de la Supervivencia Global (OS, Overall Survival) de 34,4 meses y con un perfil de seguridad aceptable.

A modo de referencia (no son estudios comparables frente a frente), los resultados más recientes de otras combinaciones de doxorubicina, como los presentados en ASCO 2019 en el estudio de fase III ANNOUNCE (doxorubicina + olaratumumab), reportaron una mediana de PFS de 6,9 meses, y una OS de 21,9 meses (ASCO 2019 LBA3)¹ .

La Dra. Patricia Pautier ha dicho: “La combinación de doxorrubicina y trabectedina constituye una terapia activa en primera línea para los pacientes con leiomiosarcoma uterino y de tejidos blandos. Los resultados en la tasa de respuesta global, la supervivencia libre de progresión y ahora de la supervivencia global son muy alentadores". Y añadió: "Están pendientes los resultados del ensayo del LMS04, un estudio aleatorio de fase III que compara esta combinación seguida de trabectedina frente a doxorubicina como agente único en primera línea para el tratamiento de leiomiosarcoma metastásico".

Todas las presentaciones de póster virtuales de ASCO estarán disponibles a petición de los participantes registrados durante 180 días desde el 29 de mayo de 2020: https://meetinglibrary.asco.org/

Early menopause in smokers linked to bladder cancer

 

Research shows that experiencing menopause before the age of 45 is associated with a higher risk of bladder cancer. This higher risk was notable if the woman is a smoker. The study, which looked at health outcomes of more than 220,000 US Nurses, is presented at the European Association of Urology congress in Barcelona. Bladder cancer is the 6th most common cancer diagnosed in Europe*. It is more common in men than in women, but women are more likely to suffer from advanced bladder cancer and are less likely to survive than men. Around 27,000 European women and 19,000 US women are diagnosed with bladder cancer each year. The US and European scientists studied the medical history of nurses who had enrolled in the Nurses’ Health Study I and II, which have been following the health outcomes of more than 220,000 US nurses since 1976. They found that women who went into menopause before the age of 45 were 45% more likely to have bladder cancer than those who had later menopause (after 50). If these women had smoked, the risk of bladder cancer was 53% greater than women who had later menopause. Around 1 woman in 20 undergoes early menopause before the age of 45, the average age at menopause is 51 in developed countries. Lead researcher Dr Mohammad Abufaraj (now working at the University of Vienna) commented: “We found that smoking women who experienced menopause before they were 45 years old had a greater risk of bladder cancer. Smoking remains the most important risk factor for bladder cancer. Our data also revealed that it is unlikely that female factors such as age when periods begin, number of pregnancies, oral contraceptive use or the use of hormone replacement therapy are associated with bladder cancer risk. Smoking is associated with earlier age at menopause thereby further increasing the risk of developing bladder cancer.” The number of cases and the number of people who die from bladder cancer varies significantly from country to country. In general, around 3 times more men than women get bladder cancer, but the mortality rate in women is around 40% higher**. There are many explanations for these differences including delay in diagnosis, genetic/epigenetic factors and hormonal factors. Dr Abufaraj added: “This study indicates that earlier age at menopause (that is, shorter reproductive life) seems to increase the risk of bladder cancer. Our primary interpretation is that a factor like smoking, which is known to correlate with earlier age at menopause, remains of grave concern as the main cause of in bladder cancer. It reinforces the warning that smoking really is harmful in ways that we might not have easily imagined.” Previous research from the same research team has shown that smoking has a dose-response relationship with prognosis in both early and advanced bladder cancer. In other words, cigarette consumption worsens outcomes such as response to therapy and mortality. Ten years after stopping smoking, this risk had returned to the same level as that of non-smokers***. Commenting, Professor Arnulf Stenzl, Chairman EAU Scientific Congress Committee (Eberhard-Karls-University in Tübingen) said: “In this long term study, smoking clearly sticks out as the underlying reason for the increased incidence of bladder cancer. However, we need to remain open to other factors causing bladder cancer, such as hormonal changes leading to earlier menopause; this work indicates that these changes may themselves be a result of long term nicotine exposure.” This is an independent comment; Professor Stenzl was not involved in this work.

Quality cancer care: not just a matter of anti-cancer medicines

ESMO, the leading professional organisation for medical oncology, shares concerns expressed in a scientific paper and reflected in the international media about the rising costs of cancer medicines.

The authors of The Journal of Oncology Practice paper used both the ESMO Magnitude of Clinical Benefit Scale (ESMO-MCBS) and ASCO’s Value Framework to assess whether the clinical benefits of novel anticancer drugs have increased over time in parallel with increasing pricing. The authors concluded that while costs of these have risen over the past decade, their clinical benefit has not improved proportionally.

The ESMO-MCBS uses a rational, structured and consistent approach to rank the level of clinically meaningful benefit that can be expected from anticancer treatments.

Prof. Elisabeth de Vries, Chair of the ESMO Cancer Medicines Committee and the ESMO-MCBS Working Group, said: “The ESMO-MCBS provides unbiased information to help guide physicians and decision makers to measure the value of drugs newly approved by the European Medicines Agency (EMA) by assessing their clinical benefit. It is an important first step in the major and ongoing task of evaluating value in cancer care which is essential for the appropriate use of limited public treasuryfunds in delivering cost-effective and more affordable cancer care.”

Prof. Josep Tabernero, ESMO President, said: “Access to anticancer medicines is an essential component of high quality cancer care, hence affordability is crucial in providing optimal treatment and patient care.” There are however many additional critical factors. “Other major considerations include the availability of highly trained practicing  oncologists, up-to-the-minute diagnostics, the necessary funding and frameworks in place to ensure correct political  research of excellence,; a holistic approach to cancer  care incorporating supportive and palliative care, and a multidisciplinary approach to best manage and treat our cancer patients” continued Tabernero.

“ESMO calls for a multi-stakeholder commitment towards ultimately ensuring access to optimal cancer care for all patients,” said Tabernero. “Sustainable cancer care is a key pillar of the ESMO 2020 Vision and we are determined to continue pursuing this goal in collaboration with our partners.”

Eisai Submits Marketing Authorisation Application to the European Medicines Agency for Lenvatinib in First-Line Hepatocellular Carcinoma

 Eisai announced it has submitted a marketing authorisation application to the European Medicines Agency (EMA) for the first-line use of lenvatinib in patients with unresectable hepatocellular carcinoma (uHCC). Patients with hepatocellular carcinoma face a poor prognosis, with a complex disease which accounts for approximately 90% of liver cancer cases worldwide.

“For a decade there has been no advance in the first-line systemic treatment of unresectable hepatocellular carcinoma in Europe,” said Professor Jeff Evans, Professor of Translational Cancer Research, University of Glasgow. “There is a significant unmet need for patients with this advanced form of liver cancer, where treatment options are limited.”

The EMA submission is based on results of the pivotal Phase III REFLECT study (Study 304). Lenvatinib was the only first-line agent to demonstrate non-inferior overall survival (OS) versus sorafenib in uHCC, with a significant and clinically meaningful improvement versus sorafenib in all secondary efficacy enpoints of progression-free survival (PFS), time to progression (TTP) and objective response rate (ORR). The REFLECT study results were presented in an oral session at this year’s American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago and will be published soon in the peer-reviewed journal The Lancet.

                                                              

“This announcement represents another important milestone for lenvatinib in difficult-to-treat cancer types,” said Gary Hendler, Chairman & CEO EMEA, Chief Commercial Officer, Oncology Business Group at Eisai. “Based on the results observed in the REFLECT trial we are looking forward to working with the EMA to bring a much-needed first-line new treatment option for liver cancer patients in Europe one step closer.” 

Lenvatinib is currently approved in the EU for the treatment of adult patients with progressive, locally advanced or metastatic, differentiated (papillary, follicular, Hürthle cell) thyroid carcinoma (DTC) refractory to radioactive iodine (RAI). Lenvatinib is also approved in combination with everolimus for the treatment of adult patients with advanced renal cell carcinoma following one prior vascular endothelial growth factor (VEGF)-targeted therapy.

Eisai is dedicated to the discovery, development and production of innovative oncology therapies that can make a difference and impact the lives of patients and their families. This passion for people is part of Eisai's human health care (hhc) mission, which strives to better understand the needs of patients and their families to increase the benefits health care provides.

  

Zoning in on specifics of Mediterranean diet for colorectal health

 The benefits of a “Mediterranean diet” (MD) are well-known when it comes to colorectal protection, but it’s hard to know specifically what elements of the diet are the healthiest.

Now a new study, presented today at the ESMO 19^th World Congress on Gastrointestinal Cancer suggests loading up on fish and fruit, and cutting back on soft drinks are the three most important things.

“We found that each one of these three choices was associated with a little more than 30% reduced odds of a person having an advanced, pre-cancerous colorectal lesion, compared to people who did not eat any of the MD components. Among people who made all three healthy choices the benefit was compounded to almost 86% reduced odds,” said Naomi Fliss Isakov, PhD fromTel-Aviv Medical Center, in Tel Aviv, Israel.

Colorectal cancer (CRC) develops from intestinal polyps and has been linked to a low-fibre diet heavy on red meat, alcohol and high-calorie foods, said Fliss Isakov.

And while the Mediterranean diet has been associated with lower rates of colorectal cancer, the definition of what elements in the diet are the most beneficial, has not always been clear.

Using dietary questionnaires from 808 people who were undergoing screening or diagnostic colonoscopies, the research team was able to dig down to look at the fine details of their daily meals.

All subjects were between 40 and 70 years old, without high risk of CRC, and answered a food frequency questionnaire.

Adherence to the MD components was defined as consumption levels above the group median for fruits, vegetables and legumes, nuts and seeds, whole grains, fish and poultry and a high ratio of monounsaturated to saturated fatty acids, as well consumption below the median of red meat, alcohol, and soft drinks.

The investigators found that compared to subjects with clear colonoscopies, those who had advanced polyps reported fewer components of the Mediterranean diet (a mean of 1.9 versus 4.5 components). Yet even consumption of two to three components of the diet, compared to none, was associated with half the odds of advanced polyps.

Odds were reduced in a dose response manner with additional MD components – meaning that the more MD components people adhered, the lower their odds of having advanced colorectal polyps.

After adjusting to account for other CRC risk factors, including other dietary components, the researchers narrowed in on high fish and fruit and low soft drinks as the best combo for reduced odds of advanced colorectal polyps.

The next step will be to see whether the MD is linked to lower risk of CRC in higher risk groups, she concluded.

Commenting on the study, ESMO spokesperson Dirk Arnold, MD, PhD, from Instituto CUF de Oncologia in Lisbon, Portugal, said “this large population-based cohort-control study impressively confirms the hypothesis of an association of colorectal polyps with diets and other life-style factors. This stands in line with other very recent findings on nutritive effects, such as the potential protective effects of nut consumption and Vitamin D supplementation which have been shown earlier this year. However, it remains to be seen whether these results are associated with reduced mortality, and it is also unclear if, and when a dietary change would be beneficial. Despite this lack of information, it makes sense to consider this diet for other health-related reasons also.”

ESMO 2019 Annual Congress to be held in Barcelona

ESMO, the leading European professional organisation for medical oncology, has announced that the ESMO 2019 Annual Congress will take place in partnership with the European Association for Cancer Research (EACR) from 27 September to 1 October 2019, at the Fira Barcelona, Spain.

The ESMO Congress is the appointment in Europe for clinicians, researchers, patient advocates, journalists and the pharmaceutical industry from all over the world to get together, learn about the latest advances in oncology and translate science into better cancer patient care.

“Two of Spain´s undeniable strengths are the quality of its research system and international cooperation in oncology. I am therefore thrilled that ESMO has, for the first time, selected Barcelona, Spain, as the global stage for the exchange and debate of translational cancer science of excellence, first announcements of potentially practice changing data, and multidisciplinary must-have conversations set to spur transformative therapies against cancer,” says Prof Josep Tabernero, ESMO President Elect, Head of the Medical Oncology Department, Vall d´Hebron University Hospital, and Director of the Vall d´Hebron Institute of Oncology (VHIO).

ESMO 2019 in Barcelona follows two congresses in Madrid in 2014 and 2017.

“It is my great pleasure to welcome the ESMO Congress in Spain again,” says Dr. Miguel Martín, President of the Sociedad Española de Oncología Médica (SEOM). “With cancer cases on the rise here and elsewhere and many unmet needs, the research presented at ESMO brings real hope for patients worldwide and we are proud that in 2019 this knowledge will be showcased in Barcelona, a cradle for cancer research.”

The ESMO 2019 programme will be developed by a committee composed of more than 300 international experts under the leadership of Scientific Co Chairs Prof Jean-Yves Blay, ESMO, and Prof Anton Berns, EACR.

The ESMO Congress currently attracts more than 22,000 oncology stakeholders from all over the world.

Christoph Tessmar, Director of the Barcelona Convention Bureau says: “We are delighted to host the ESMO Congress in Barcelona for the first time. Our attractive destination, as well as our long tradition of hosting important congresses, will guarantee a huge success for ESMO 2019. The Barcelona Convention Bureau and all its Partners will do their very best to make this a congress to remember for ESMO 2019 participants.”

ESMO invites all oncology stakeholders: researchers, clinicians, industry partners, patient advocates and members of the press to mark their calendars for ESMO 2019 in Barcelona.